Biologists pinpoint how common virus triggers multiple sclerosis

For years, a common virus has been implicated in the development of multiple sclerosis, a disease in which the body’s immune system attacks nerve cells in the brain and spinal cord. Now, researchers have uncovered how the virus triggers the immune system. They also reveal how an immunotherapy treatment can prevent relapses and slow disease progression¹. The results are published today in Science Translational Medicine.

The findings are a sign that scientists are starting to get to the bottom of how Epstein–Barr virus drives the development of multiple sclerosis (MS), says Emily Edwards, a rare-diseases researcher at Monash University in Melbourne, Australia.

Epstein–Barr virus is a herpesvirus present in about 90% of the global population. For most people, the infection is relatively harmless and does not lead to MS. But for a subset of the population, it is “well established” that Epstein–Barr virus is one of the main causes of MS, according to study co-author Natalia Drosu, a neurology researcher at the Massachusetts General Hospital in Boston. But how the virus triggers the condition was unknown until now.

In MS, immune cells attack the protective myelin sheath that surrounds nerves, leading to vision problems and difficulty walking. It affects around 2.9 million people globally. Currently, people with MS can take drugs to slow the disease’s progression and reduce the frequency and severity of episodes in which symptoms worsen, but there is no cure.

Immune-system response

Drosu says that she and her team wanted to investigate which parts of the immune system respond to Epstein–Barr virus. They showed that immune T cell activity was twice as high in people with MS compared with healthy control individuals. When the researchers selectively depleted the levels of various kinds of T cell in the participants, they found that people’s immune responsiveness to the virus decreased markedly once a specific type known as a CD4⁺ T cell was removed, indicating that this group drives the response.

Drosu says that another reason they focused on CD4⁺ T cells was because a drug used to treat MS, called frexalimab, acts on them. The treatment reduces inflammation and nerve damage by blocking CD4⁺ T-cell activity. “That suggested we should look at this immune response in particular,” she explains. Another class of existing drugs called anti-CD20 therapies also reduce the immune system’s responsiveness to Epstein–Barr virus, but it was unclear how, the study notes.

To find out, the researchers measured the levels of CD4⁺ T cells in the bodies of 60 people with MS before and six months after starting an anti-CD20 treatment. They found that the levels of CD4⁺ T cells in the participant’s bodies had decreased by about 2.5 times after the measurement period. The team validated their results in a second group of people and found that the reduction in T-cell levels persisted for up to a year.

Another group of people who received anti-CD20 treatment also had lower levels of Epstein–Barr virus in their saliva compared with healthy people and individuals with untreated MS.

Edwards says that this suggests that the treatment reduces the amount of viral activity in the body. Anti-CD20 therapy work by binding to and destroying another type of immune cell, called B cells, which are infected. Because there are fewer B cells, the CD4⁺ T cells have fewer stimuli to respond to, leading to a reduced immune response. “That shows the importance of both of these groups of immune cells in driving disease, and how we can moderate that with immunotherapies to potentially reduce disease severity,” adds Edwards.